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A S Leonard

Publications and source records attributed to A S Leonard.

At least 19 recordsLinked to original sources
PubMed2002

Liver and circulating NK1.1(+)CD3(-) cells are increased in infection with attenuated Salmonella typhimurium and are associated with reduced tumor in murine liver cancer.

An attenuated (DeltacyA, Deltacrp) strain of Salmonella typhimurium (chi4550) containing a gene for human IL-2 (chi4550pIL2) reduces hepatic tumor burden when orally inoculated into mice with liver cancer; however, wild-type S. typhimurium is also associated with cancer regression. Therefore, experiments were designed to clarify the invasiveness and the anti-tumor properties of three strains of S. typhimurium. S. typhimurium chi4550pIL2, chi4550, or wild type (WT) was incubated with mature Caco-2 and HT-29 enterocytes, and S. typhimurium internalization was assessed. For infectivity experiments, mice were orally inoculated with saline or 10(9)S. typhimurium chi4550pIL2, chi4550, or WT; 48 h later mice were sacrificed for analysis of cecal bacteria and S. typhimurium translocation to mesenteric lymph nodes. For experiments involving tumor implantation, four groups were studied: saline control, tumor alone, chi4550pIL2+tumor, and chi4550+tumor. Mice were orally inoculated with saline or S. typhimurium and underwent laparotomy 24 h later with 5 x 10(4) MCA38 murine adenocarcinoma cells injected into the spleen. On day 14, liver tumors were counted and peripheral blood and hepatic lymphocyte populations were analyzed by FACScan. Attenuated S. typhimurium exhibited decreased internalization by cultured enterocytes and decreased infectivity after oral inoculation. Mice treated with chi4550pIL2 or chi4550 had fewer liver tumors and increased populations of hepatic and circulating NK1.1(+)CD3(-) lymphocytes compared to mice treated with saline (P < 0.01). These data suggest that attenuated S. typhimurium may have an application as an anti-tumor agent.

Animals↗
PubMed2001

Interaction with the NMDA receptor locks CaMKII in an active conformation.

Calcium- and calmodulin-dependent protein kinase II (CaMKII) and glutamate receptors are integrally involved in forms of synaptic plasticity that may underlie learning and memory. In the simplest model for long-term potentiation, CaMKII is activated by Ca2+ influx through NMDA (N-methyl-D-aspartate) receptors and then potentiates synaptic efficacy by inducing synaptic insertion and increased single-channel conductance of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors. Here we show that regulated CaMKII interaction with two sites on the NMDA receptor subunit NR2B provides a mechanism for the glutamate-induced translocation of the kinase to the synapse in hippocampal neurons. This interaction can lead to additional forms of potentiation by: facilitated CaMKII response to synaptic Ca2+; suppression of inhibitory autophosphorylation of CaMKII; and, most notably, direct generation of sustained Ca2+/calmodulin (CaM)-independent (autonomous) kinase activity by a mechanism that is independent of the phosphorylation state. Furthermore, the interaction leads to trapping of CaM that may reduce down-regulation of NMDA receptor activity. CaMKII-NR2B interaction may be prototypical for direct activation of a kinase by its targeting protein.

Animals↗
PubMed2000

SAP97 concentrates at the postsynaptic density in cerebral cortex.

SAP97, a PDZ-containing protein, is reported to concentrate in axon terminals, where its function remains unknown. Using highly specific new antibodies, we show that SAP97 in rat cerebral cortex is associated with heteromeric AMPA receptors via a selective biochemical interaction between SAP97 and the GluR1 subunit. Using light and electron microscopic immunocytochemistry, we demonstrate cellular and synaptic colocalization of SAP97 and GluR1, and show that SAP97 concentrates at synapses that contain GluR1 but not necessarily GluR2 or GluR3. Using quantitative postembedding immunogold electron microscopy, we find that SAP97 is at highest concentration within the postsynaptic density of asymmetric synapses. These data suggest that SAP97 may help to anchor GluR1-containing AMPA receptors at the synapse. As a multifunctional scaffolding protein, SAP97 may organize components of AMPA-related intracellular signalling pathways, including those associated with calcium-permeable homomeric GluR1 channels.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Calcium/calmodulin-dependent protein kinase II is associated with the N-methyl-D-aspartate receptor.

The molecular basis of long-term potentiation (LTP), a long-lasting change in synaptic transmission, is of fundamental interest because of its implication in learning. Usually LTP depends on Ca2+ influx through postsynaptic N-methyl-D-aspartate (NMDA)-type glutamate receptors and subsequent activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII). For a molecular understanding of LTP it is crucial to know how CaMKII is localized to its postsynaptic targets because protein kinases often are targeted to their substrates by adapter proteins. Here we show that CaMKII directly binds to the NMDA receptor subunits NR1 and NR2B. Moreover, activation of CaMKIIalpha by stimulation of NMDA receptors in forebrain slices increase this association. This interaction places CaMKII not only proximal to a major source of Ca2+ influx but also close to alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptors, which become phosphorylated upon stimulation of NMDA receptors in these forebrain slices. Identification of the postsynaptic adapter for CaMKII fills a critical gap in the understanding of LTP because CaMKII-mediated phosphorylation of AMPA receptors is an important step during LTP.

Animals↗
PubMed1998

SAP97 is associated with the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor GluR1 subunit.

Rapid glutamatergic synaptic transmission is mediated by ionotropic glutamate receptors and depends on their precise localization at postsynaptic membranes opposing the presynaptic neurotransmitter release sites. Postsynaptic localization of N-methyl-D-aspartate-type glutamate receptors may be mediated by the synapse-associated proteins (SAPs) SAP90, SAP102, and chapsyn-110. SAPs contain three PDZ domains that can interact with the C termini of proteins such as N-methyl-D-aspartate receptor subunits that carry a serine or threonine at the -2 position and a valine, isoleucine, or leucine at the very C terminus (position 0). We now show that SAP97, a SAP whose function at the synapse has been unclear, is associated with alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptors. AMPA receptors are probably tetramers and are formed by two or more of the four AMPA receptor subunits GluR1-4. GluR1 possesses a C-terminal consensus sequence for interactions with PDZ domains of SAPs. SAP97 was present in AMPA receptor complexes immunoprecipitated from detergent extracts of rat brain. After treatment of rat brain membrane fractions with the cross-linker dithiobis(succinimidylpropionate) and solubilization with sodium dodecylsulfate, SAP97 was associated with GluR1 but not GluR2 or GluR3. In vitro experiments with recombinant proteins indicate that SAP97 specifically associates with the C terminus of GluR1 but not other AMPA receptor subunits. Our findings suggest that SAP97 may be involved in localizing AMPA receptors at postsynaptic sites through its interaction with the GluR1 subunit.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Complications and risks of central venous catheter placement in children.

BACKGROUND: Since Aubaniac's first description in 1952, the use of central venous catheters has increased dramatically; they are now considered commonplace. Placement of these catheters, however, has an associated risk of morbidity and mortality. In most cases, this risk is outweighted by the benefit gained, especially when long-term access to the central venous system is needed for multiple transfusions, chemotherapy, antibiotics, or parenteral nutrition. A large number of central venous catheters are placed in children at our institution, usually by interns and residents. METHODS: To identify associated risks and complications, we reviewed the records of 1435 consecutive catheterizations in children over a 10-year period. Data collected included age, sex, site of catheterization, type of catheter, primary disease, prior catheterizations, indication for placement, failed attempts, number of attempts, catheter misplacement, level of physician training, new needle punctures, and complications. We then used logistic regression analysis to identify independent risk factors for complications. RESULTS: We noted 39 (3.1%) perioperative complications, including 19 (1.5%) arterial punctures, 10 (0.8%) pneumothoraces, 6 (0.5%) hemothoraces, 2 (0.2%) cases of superior vena cava syndrome, 1 (0.1%) episode of ventricular fibrillation that required cardioversion, and 1 episode of bleeding that required a cutaneous suture. Univariate analysis revealed that catheters placed in a subclavian vein (vs all other sites combined, P < .01) were less likely to have an associated complication. In addition, multiple attempts (vs success on first attempt, P < .0001), failed attempt (vs success at initial site, P < .0001), catheter misplacement (vs proper initial position, P < .01), and prior catheterizations (vs no prior catheterization, P < .0005) were associated with complications. Logistic regression revealed multiple attempts (vs success on first attempt, odds ratio (OR) = 5.4), failed attempt (vs success at initial site, OR = 5.2), and catheter misplacement (vs proper initial position, OR = 6.9) to be independent risk factors for complications. Age, sex, type of catheter, primary disease, indication for placement, and level of physician training (intern or resident vs staff) were not associated with complications. CONCLUSIONS: Central venous catheterization in children is relatively safe, with only a 3.2% complication rate and no mortality in our series.

Adolescent↗
PubMed1997

Cyclic AMP-dependent protein kinase and protein kinase C phosphorylate N-methyl-D-aspartate receptors at different sites.

Ca2+ influx through N-methyl-D-aspartate (NMDA)-type glutamate receptors plays a pivotal role in synaptic plasticity during brain development as well as in mature brain. Cyclic AMP-dependent protein kinase (PKA) and members of the protein kinase C (PKC) family are also essential for various forms of synaptic plasticity and regulate the activity of different ion channels including NMDA and non-NMDA receptors. We now demonstrate that PKA and various PKC isoforms phosphorylate the NMDA receptor in vitro. The stoichiometry of [32P]phosphate incorporation per [3H]MK-801 binding site is greater than 1 for both PKA and PKC. Double immunoprecipitation experiments show that all three NMDA receptor subunits that are prevalent in the cortical structures, NR1, NR2A, and NR2B, are substrates for PKA as well as PKC. Two-dimensional phosphopeptide mapping reveals that the major phosphorylation sites for PKA and PKC differ for all three subunits. We provide evidence that some if not most of these sites are phosphorylated in the central nervous system of rats in vivo. The results presented in this article together with earlier electrophysiological experiments demonstrating that PKA and PKC activation increases the activity of NMDA receptors indicate that NMDA receptor potentiation can be mediated by direct phosphorylation by PKA and PKC. Collectively, these results strongly suggest that NMDA receptor functions such as control of neuronal development or expression of synaptic plasticity are modulated by PKA- and PKC-mediated phosphorylation of NMDA receptors.

Adenosine Triphosphate↗
PubMed1997

Adoptive transfer of anti-CD3-activated CD4+ T cells plus cyclophosphamide and liposome-encapsulated interleukin-2 cure murine MC-38 and 3LL tumors and establish tumor-specific immunity.

The infusion of anti-CD3-activated murine T cells plus interleukin-2 (IL-2) exerts antitumor effects against several tumors in murine immunotherapy models. This study compares the therapeutic efficacy of anti-CD3-activated CD4+ or CD8+ T-cell subsets, when given with cyclophosphamide (Cy) and liposome-encapsulated IL-2 (L-IL2) in a murine model. C57BL/6 mice bearing subcutaneous (S.C.) MC-38 colon adenocarcinoma, 3LL Lewis lung carcinoma, or 38C13 lymphoma for 7 to 14 days were pretreated with low-dose intraperitoneal (I.P.) Cy before intravenous (I.V.) injection of anti-CD3-activated T cells or T-cell subsets. Cell administration was followed by I.P. administration of L-IL2 for 5 days. Mice receiving activated CD4+ T cells showed significantly reduced tumor growth or complete remissions with prolonged disease-free survival in MC-38, 3LL, and 38C13. The timing of Cy doses in relation to adoptive transfer was critical in obtaining the optimal antitumor effect by CD4+ cells. Injecting Cy 4 days before the infusion of CD4+ cells greatly enhanced the antitumor effect of the CD4+ cells and improved survival of the mice compared with other Cy regimens. C57BL/6 mice cured of MC-38 after treatment with CD4+ T cells developed tumor-type immunologic memory as demonstrated by their ability to reject rechallenges with MC-38, but not 3LL. Similarly, mice cured of 3LL tumors rejected rechallenges of 3LL, but not MC-38. The immunologic memory could be transferred with an I.V. injection of splenocytes from mice cured of MC-38 or 3LL. No cytotoxic T-lymphocyte activity was detected in T cells or T-cell subsets from mice cured of MC-38 or 3LL. Increased IL-2 and interferon-gamma (IFN-gamma) production was observed from CD4+ subsets in cured animals when stimulated in vitro with the original tumor, but not with an unrelated syngeneic tumor. These results suggest that tumor-specific immunity can be achieved in vivo with anti-CD3-stimulated CD4+ T cells in this cellular therapy model.

Adenocarcinoma↗
PubMed1997

Antitumor mechanisms of attenuated Salmonella typhimurium containing the gene for human interleukin-2: a novel antitumor agent?

Currently, there is no long-term effective treatment for unresectable hepatic malignancies. Salmonella species are known to naturally track to the liver during active infection. To develop a biological vector for delivery of interleukin-2 (IL-2) to the liver for antitumor purposes, the thi 4550 attenuated strain of Salmonella typhimurium was used as a vector for IL-2. The gene for human IL-2 was cloned into plasmid pYA292 and inserted into the attenuated S typhimurium and renamed (thi 4550(pIL-2)]. MCA-38 murine adenocarcinoma cells were injected intrasplenically into C57BL/6 mice to produce hepatic metastases that were subsequently enumerated after 12 days. We previously have demonstrated that the thi 4550(pIL-2) produces biologically active IL-2 and that a single gavage feeding of 10(7) thi 4550(pIL-2) significantly reduced the number of hepatic metastases when compared with animals fed salmonella lacking the IL-2 gene or nontreated controls. The aims of the current studies were to determine which host effector cell populations were responsible for the antitumor effect seen with thi 4550(pIL-2) by depletion of natural killer (NK), cytotoxic T lymphocytes (CD8+), T helper (CD4+) cells, and Kupffer cells. Multiple experiments were conducted for each host effector cell population depleted. We found a consistent reduction in the mean number of hepatic metastases in animals fed thi 4550(pIL-2) (55.6 metastases; n = 54) when compared with controls (162.3 metastases; n = 53) (P < .0001). Depletion of NK cells and CD8+ T cells significantly inhibited the antitumor effect of thi 4550(pIL-2) (analysis of variance [ANOVA], P < .01). Elimination of CD4+ T cells and Kupffer cells had no significant impact on the antitumor effect of thi 4550(pIL-2) (ANOVA, P value was not significant). Salmonella IL-2 may represent a novel form of in vivo biotherapy for unresectable hepatic malignancies that employs the oral route of administration. Furthermore, both NK cells or CD8+ cells are required for the antitumor effect seen while CD4+ T cells and Kupffer cells do not appear to be as essential.

Adenosarcoma↗
PubMed1997

Patterns of hepatic and splenic colonization by an attenuated strain of Salmonella typhimurium containing the gene for human interleukin-2: a novel anti-tumor agent.

Currently, there is no effective treatment for unresectable hepatic malignancies. Salmonella sp. are known to naturally track to the liver during active infection. A live biological vector was developed for delivery of Interleukin-2 (IL-2) to the liver for anti-tumor purposes. The avirulent and highly immunogenic c4550 strain of Salmonella typhimurium was used to express the IL-2 protein [renamed c4550(pIL-2)]. We have previously demonstrated that the c4550(pIL-2) produces biologically active IL-2 (up to 46.2 IU/ml) and that a single gavage feeding of 10(7) colony forming units (cfu) of c4550(pIL-2) significantly reduced the number of hepatic metastases when compared to animals fed salmonella lacking the IL-2 gene or non-treated controls. The goal of the current studies was to determine the pattern of splenic and hepatic colonization of Salmonella-IL2. Hepatic and splenic colonization was determined following administration of 10(7) cfu of c4550(pIL-2) and c4550(pYA292) via a single gavage feeding to C57BL/6 mice. Five experiments of antibiotic regimen administration were conducted where splenic and hepatic homogenates were cultured after 14 days of parenteral and/or oral antibiotics. The natural history of hepatic and splenic colonization was also determined for animals without antibiotic treatment. Despite administration of various antibiotic regimens using different routes, eradication of salmonella with and without IL-2 was not achieved. Salmonella, however, was not cultured from hepatic and splenic tissue at 4 months after a single gavage feeding of salmonella with no specific treatment. In conclusion, oral administration of c4550(pIL-2) may represent a novel form of in vivo biotherapy for unresectable hepatic malignancies. Antibiotics do not accelerate eradication of this bacteria and it appears that c4550(pIL-2) follows the natural pathophysiological of salmonella infection in which eradication from the splenic and hepatic tissue occurs over a period of 2-4 months.

Animals↗
PubMed1996

Paraplegia resulting from vessel ligation.

STUDY DESIGN: This is a retrospective review of clinical records for evidence of paraplegia specifically resulting from segmental vessel ligation during anterior spinal surgery. OBJECTIVES: To determine the precise risk rate, and to potentially identify risk factors. SUMMARY OF BACKGROUND DATA: Although many authors have alluded to this risk, the exact risk rate and risk factors have never been identified. METHODS: All patients having an anterior approach involving T1-L3 were reviewed. The two reviewers were not involved in any of the surgeries. The 1197 cases were consecutive from 1967 to 1991. RESULTS: There were no paralyses. CONCLUSIONS: There would appear to be virtually no risk to segmental vessel ligation provided: 1) vessel ligation is unilateral, 2) done on the convexity of a scoliosis, 3) ligated at midvertebral body level, and 4) hypotensive anesthesia is avoided. Soft clamping with somatosensory-evoked potential monitoring does not appear justified.

Adult↗
PubMed1996

Islet Autotransplantation after total pancreatectomy in a child.

Islet autotransplantation can prevent surgically induced diabetes after total pancreatectomy in adults; however, the efficacy of this procedure has not been established in children. The authors report the case of a 12-year-old boy who underwent total pancreatectomy and islet autotransplantation for intractable pain caused by idiopathic chronic pancreatitis. Islets were prepared from the excised pancreas by collagenase digestion and mechanical dispersion. The resultant preparation, containing 109,500 islets, was injected into the recipient's liver via the portal vein. No complication from the pancreatectomy or transplant occurred. Postoperatively, the patient had complete relief of abdominal pain. He remained insulin-independent, with normal fasting blood glucose and hemoglobin A1c levels, for 21/2 years. Preoperatively, the acute insulin response and the rate of glucose disappearance (Kg) were 213 microU/mL and 2.14% (respectively) after intravenous administration of 20 g of glucose. Although lower than pretransplantation values, both insulin response and Kg remained normal at 4 months (88 microU/mL; Kg, 1.01%); however, these decreased further, to below normal, by 2 years posttransplantation (10 microU/mL; Kg, 0.67%). Two-and-a-half years after transplantation, fasting hyperglycemia (> 200 mg/dL) was evident, and the patient was begun on exogenous insulin. Five years posttransplantation he remains insulin-dependent with a fasting serum C-peptide level of 0.20 ng/mL, which increased to 0.35 ng/mL in response to intravenous arginine, indicating sustained islet function. During the documented decreases in insulin secretion and Kg posttransplantation, the patient's body weight increased by 65% (from 34 to 56 kg) as a result of normal growth; the number of transplanted islets relative to body mass decreased accordingly, from 3,200 to 1,950 islets per kilogram of body weight. In this case, the number of islets transplanted likely could not meet the increased insulin demands of the larger body mass. Thus, exogenous insulin supplementation was needed to prevent hyperglycemia. In conclusion, insulin independence was initially established in a child by islet autotransplantation after total pancreatectomy. The failure of the islets to maintain normoglycemia long-term suggests that a sufficient number must be transplanted (to meet the demands of normal growth and development) for sustained insulin independence.

Blood Glucose↗
PubMed1996

Attenuated Salmonella typhimurium containing interleukin-2 decreases MC-38 hepatic metastases: a novel anti-tumor agent.

Currently, there is no long-term effective treatment for unresectable hepatic malignancies. Salmonella sp. are known to naturally track to the liver during active infection. To develop a biological vector for delivery of Interleukin-2 (IL-2) to the liver for anti-tumor purposes, the avirulent and highly immunogenic chi 4550 strain of Salmonella typhimurium was used as a vector for IL-2. The gene for human IL-2 was cloned into plasmid pYA292 (renamed pIL-2) and inserted into the attenuated Salmonella typhimurium and renamed [chi 4550 (pIL-2)]. This transformant was found to produced biologically active IL-2 demonstrated by NK cell activation in a 4 hour chromium release cytotoxicity assay. To determine anti-tumor potential, MCA-38 murine adenocarcinoma cells were injected intrasplenically into C57BL/6 mice to produce hepatic metastases and metastases were subsequently enumerated after 12 days. Statistical significance was determined by ANOVA with Fisher's test for significance. Hepatic metastases enumerated by blinded observers revealed that the mean number of metastases was 106.4 in control mice, 103.7 in mice gavage fed attenuated salmonella without IL-2 [chi 4550(pYA292)], and 44.3 in mice fed the chi 4550(pIL2); (ANOVA: p < 0.01). Culture of livers and spleens in mice administered a single gavage dose of salmonella demonstrated persistent colonization for up to 4 weeks. No observable toxicity was seen to either IL-2 or salmonella. These studies demonstrate that the chi 4550(pIL2) is a novel form of in vivo biotherapy which produces biologically active IL-2 and employs the oral route of administration to stimulate an immune response against malignancy in the liver.

Animals↗
PubMed1995

Knotted bowel: small-bowel obstruction from coiled peritoneal shunt catheters. Report of two cases.

Knotting of a peritoneal catheter around a loop of bowel is a rare occurrence, which may lead to bowel obstruction. The incomplete removal of two ventriculoperitoneal shunts resulted in two cases of iatrogenically knotted peritoneal catheters. One patient underwent a laparotomy for relief of obstruction and the other was successfully treated by uncoiling the catheter by means of a wire passed into its lumen. A plan for management of a knotted peritoneal catheter is outlined.

Cerebrospinal Fluid Shunts↗
PubMed1994

Light and electron microscopic features of the liver in mucopolysaccharidosis.

The mucopolysaccharidosis (MPS) diseases lead to the accumulation of glycosaminoglycan in many tissues. In this study 19 MPS I, one MPS II, five MPS III, and two MPS VI patients underwent liver biopsy for light and electron microscopic examination. Electron microscopy was performed for all 27 specimens. Twenty-six specimens were studied by light microscopy, and the slides were stained with colloidal iron and alcian blue in 26 and six biopsy specimens, respectively. By hematoxylin-eosin stain 20 of 26 cases showed hepatocellular dilatation with rarefaction of the cytoplasm; the Kupffer cells were unremarkable. Twenty-four and 25 of the 26 biopsy specimens showed substantial colloidal iron staining of hepatocytes and Kupffer cells, respectively. The six biopsy specimens prepared with alcian blue stain showed no reactivity of any cell type. Electron microscopy revealed characteristic membrane-bound inclusions within the hepatocytes and Kupffer cells of all 27 biopsy specimens. Of 19 cases in which Ito cells were identified, 18 included cells containing similar inclusions. Twenty of 27 biopsy specimens also demonstrated the hepatocellular accumulation of lipid droplets. Although there were no absolute distinguishing features among the various MPS diseases, the two MPS VI cases showed glycosaminoglycan inclusions that were fewer in number, smaller, and contained more abundant lipofusion than those associated with the other MPS types.

Adolescent↗
PubMed1993

Children with mucopolysaccharidosis: perioperative care, morbidity, mortality, and new findings.

The perioperative care, morbidity, and mortality in 30 patients with mucopolysaccharidosis (MPS) are presented. They underwent a detailed preoperative assessment and were anesthetized 141 times. An intravenous induction technique was used in most patients. It was easier to see the vocal cords, during laryngoscopy, in children with Hurler syndrome (HS) when they were younger (23 v 41 months, P < or = .01) and smaller (12 v 15 kg, P < or = .05). Preoperative obstructive breathing was associated with a significantly higher incidence of postextubation obstruction (P < or = .05). A total of 28 children underwent bone marrow transplantation (BMT); this reversed upper airway obstruction and also reversed intracranial hypertension. In children with HS, the incidence of odontoid dysplasia was 94%; 38% demonstrated anterior C1-C2 subluxation. Head and neck manipulation was limited in children with cervical spine defects. None of the 30 patients experienced spinal cord morbidity. One child suffered an intraoperative stroke; another, pulmonary edema. Severe and extensive coronary obstruction was responsible for 2 intraoperative deaths. Coronary angiography underestimated coronary artery disease.

Adolescent↗
PubMed1993

Aggressive metastasectomy for pulmonic sarcomatous metastases: a follow-up study.

Pulmonary metastases are the primary cause of death due to bone and soft tissue sarcomas. We have previously shown that an aggressive approach and a new technique of multiple pulmonary metastasectomies have resulted in improved survival for patients with pulmonary metastases. In this follow-up study, an expanded database of patients was retrospectively analyzed to determine survivability as well as to evaluate potential prognostic indicators. Forty-nine patients, 26 of whom had osteogenic sarcoma (OGS), were evaluated. A number of patients had been referred from other institutions where their disease had been considered inoperable because it was extensive or recurrent. Using lateral thoracotomies exclusively, employment of a laser technique, and excision of minimal pulmonary parenchymal tissue, we performed aggressive metastasectomy. A mean of 3.0 thoracotomies was performed, in which an average of 10.2 nodules per thoracotomy were excised. Operative morbidity and mortality were minimal. The disease-free interval, the number of nodules resected, the number of thoracotomies performed, and the size of the nodules were evaluated as potential prognostic indicators. Statistically significant correlation could be established only for the size of the nodules resected. The 5-year survival rate for all patients was 39%; it was 24% for patients with OGS and 71% for those without OGS. Aggressive surgical resection of pulmonary metastases from bone and soft tissue sarcoma should be considered when there is control of local disease, no evidence of extrapulmonary metastasis, and adequate post-resection pulmonary reserve. The presence of bilateral, extensive, or recurrent disease is not a contraindication to thoracotomy. Aggressive resection of multiple nodules and improved chemotherapy appear to prolong survival of these patients when compared with survival rates of historical control subjects.

Adolescent↗